Osteoporosis is a debilitating illness and is a major health problem in elderly women. Two major factors have limited the study of osteroporsis - the inability to detect the disease in an early stage and the heterogeneous nature of the patients affected. Women with prolactin secreting pituitary tumors have decreased bone mineral and for the most part these tumors affect young women. This relatively uniform group of young individuals affords an opportunity to study osteopenia in an early stage and to analyze factors that may cause bone loss in older women. The goal of this project is to begin to elucidate the mechanisms of osteopenia in women with hyperprolactinemic amenorrhea and to determine if pathogenetic mechanisms thought to be responsible for postmenopausal and senile osteoporosis are operative in younger women. We will use serial determinations of spinal and forearm bone mineral to determine rates of bone loss in healthy subjects, in amenorrheic women with and without hyperprolactinemia and in postmenopausal women. We will use calcium balance studies, urinary hydroxyproline determinations and bone histomorphometry as indices of bone turnover and will determine whether normalization of serum prolactin and restoration of menstrual cycles is associated with a change in these biochemical indices. We will utilize parathyroid hormone infusions to determine whether osteopenia is due to enhanced sensitivity of bone to PTH or whether decreased renal production of 1,25 (OH)2 vitamin D and calcium malabsorption are the major factors in bone loss. Finally, we will determine if normalization of serum prolactin and menstrual cycles is associated with prevention or reversal of bone loss. The identification of a factor or factors that might contribute to the development of osteoporosis in young womem would provide insight into mechanisms that may have important application to the prevention of this illness in the elderly.